Genome wide association for substance dependence: convergent results from epidemiologic and research volunteer samples

<p>Abstract</p> <p>Background</p> <p>Dependences on addictive substances are substantially-heritable complex disorders whose molecular genetic bases have been partially elucidated by studies that have largely focused on research volunteers, including those recruited in Baltimore. Maryland. Subjects recruited from the Baltimore site of the Epidemiological Catchment Area (ECA) study provide a potentially-useful comparison group for possible confounding features that might arise from selecting research volunteer samples of substance dependent and control individuals. We now report novel SNP (single nucleotide polymorphism) genome wide association (GWA) results for vulnerability to substance dependence in ECA participants, who were initially ascertained as members of a probability sample from Baltimore, and compare the results to those from ethnically-matched Baltimore research volunteers.</p> <p>Results</p> <p>We identify substantial overlap between the home address zip codes reported by members of these two samples. We find overlapping clusters of SNPs whose allele frequencies differ with nominal significance between substance dependent <it>vs </it>control individuals in both samples. These overlapping clusters of nominally-positive SNPs identify 172 genes in ways that are never found by chance in Monte Carlo simulation studies. Comparison with data from human expressed sequence tags suggests that these genes are expressed in brain, especially in hippocampus and amygdala, to extents that are greater than chance.</p> <p>Conclusion</p> <p>The convergent results from these probability sample and research volunteer sample datasets support prior genome wide association results. They fail to support the idea that large portions of the molecular genetic results for vulnerability to substance dependence derive from factors that are limited to research volunteers.</p

Ethical and legal implications of whole genome and whole exome sequencing in African populations

BACKGROUND: Rapid advances in high throughput genomic technologies and next generation sequencing are making medical genomic research more readily accessible and affordable, including the sequencing of patient and control whole genomes and exomes in order to elucidate genetic factors underlying disease. Over the next five years, the Human Heredity and Health in Africa (H3Africa) Initiative, funded by the Wellcome Trust (United Kingdom) and the National Institutes of Health (United States of America), will contribute greatly towards sequencing of numerous African samples for biomedical research. DISCUSSION: Funding agencies and journals often require submission of genomic data from research participants to databases that allow open or controlled data access for all investigators. Access to such genotype-phenotype and pedigree data, however, needs careful control in order to prevent identification of individuals or families. This is particularly the case in Africa, where many researchers and their patients are inexperienced in the ethical issues accompanying whole genome and exome research; and where an historical unidirectional flow of samples and data out of Africa has created a sense of exploitation and distrust. In the current study, we analysed the implications of the anticipated surge of next generation sequencing data in Africa and the subsequent data sharing concepts on the protection of privacy of research subjects. We performed a retrospective analysis of the informed consent process for the continent and the rest-of-the-world and examined relevant legislation, both current and proposed. We investigated the following issues: (i) informed consent, including guidelines for performing culturally-sensitive next generation sequencing research in Africa and availability of suitable informed consent documents; (ii) data security and subject privacy whilst practicing data sharing; (iii) conveying the implications of such concepts to research participants in resource limited settings. SUMMARY: We conclude that, in order to meet the unique requirements of performing next generation sequencing-related research in African populations, novel approaches to the informed consent process are required. This will help to avoid infringement of privacy of individual subjects as well as to ensure that informed consent adheres to acceptable data protection levels with regard to use and transfer of such information

Tratamento cirúrgico da ginecomastia com pedículos lateral e medial

Ginecomastia é o aumento da mama masculina que pode acometer até 65% dos indivíduos deste sexo na fase infanto-puberal, compreendida entre 13 e 16 anos. Tem como principais causas hepatite ou cirrose hepática, carcinoma ou doenças inflamatórias pulmonares crônicas, carcinomas ou disfunções testiculares, tumores glandulares (pituitária, supra-renal), alterações dos níveis séricos de testosterona, síndromes genéticas (síndrome de Klinefelter, p.ex.), uso de drogas como heroína, maconha ou anabolizantes e hanseníase. Podemos classificar a ginecomastia quanto ao volume, quanto aos tecidos que a compõem (gordurosa ou pseudoginecomastia, glandular e mista), ou quanto ao tratamento necessário para sua correção cirúrgica (pequena, moderada e grave). O tratamento das formas mais graves de ginecomastia é muito diferente daquele aplicado às formas mais suaves, pois nas formas graves, além da ressecção dos tecidos gorduroso e glandular, existe a necessidade de ressecção da pele em excesso e o reposicionamento do complexo aréolo-mamilar. O objetivo deste trabalho é descrever uma técnica cirúrgica específica para estes pacientes portadores de formas graves de ginecomastia, através de dois pedículos dermogordurosos, um lateral e um medial, com aproximadamente 2cm de espessura, mantendo assim a nutrição do complexo aréolo-mamilar. Esses pedículos são delimitados entre as bissetrizes dos quadrantes súpero-lateral e ínfero-lateral, e súpero-medial e ínfero-medial, tendo o mamilo como vértice. Na área de pele excessiva periareolar, obtida através do pinçamento interdigital, é realizada a desepidermização dos pedículos lateral e medial e ressecção de toda pele e tecido celular subcutâneo até a fáscia peitoral nas regiões superior e inferior aos pedículos; a síntese é realizada em dois planos, sendo periareolar a cicatriz resultante. Foram operados com esta técnica vinte pacientes com forma grave de ginecomastia, com média etária de 23,3 anos; sendo seis pacientes da raça negra. O bom posicionamento do complexo aréolo-mamilar e uma cicatriz periareolar resultante, bem como a retirada de conteúdo suficiente, foram as principais vantagens observadas. Como complicações, tivemos assimetria das placas aréolo-mamilares em dois casos, nos quais havia acentuada diferença entre os dois lados na avaliação pré-operatória; cicatrização hipertrófica em um paciente da raça negra, cuja cicatriz foi atenuada com injeções intracicatriciais de triancinolona; necrose parcial de aréola em um caso, cuja ferida cicatrizou por segunda intenção, dispensando qualquer tratamento local posterior; deiscência de sutura periareolar em um caso, no qual foi feita a ressutura, com bom resultado, e quatro pacientes apresentaram coleção sero-hemática subcutânea, que foram drenadas e não apresentaram recidiva

Human genetic research: emerging trends in ethics.

Genetic research has moved from Mendelian genetics to sequence maps to the study of natural human genetic variation at the level of the genome. This past decade of discovery has been accompanied by a shift in emphasis towards the ethical principles of reciprocity, mutuality, solidarity, citizenry and universality